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1.
J Clin Neurosci ; 75: 176-180, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32217048

RESUMEN

Data indexing the contribution of various immuno-inflammatory components in the cerebrospinal fluid (CSF) towards the pathophysiology of Guillain Barré Syndrome (GBS) are limited. Th17 pathway plays crucial role in many immune mediated disorders of the nervous system. This study was aimed at exploring the role of Th17 pathway related cytokines in the CSF of patients with GBS. Levels of multiple key cytokines of Th17 pathway in CSF of patients with GBS (N = 37) and controls (N = 37) were examined in this prospective study using Bio-plex Pro Human Th17 cytokine assays in a Multiplex Suspension Array platform. The findings were correlated with clinical features and electrophysiological subtypes. Three key cytokines of Th17 pathway (IL-6, IL-17A and IL-22) were significantly elevated in CSF of patients with GBS as compared to controls. There was a positive correlation between the levels of IL-6 and IL-17A as well as between the levels of IL-17A and IL-22 in the CSF of patients with GBS. The CSF levels of IL-6 and IL-22 were negatively correlated with the duration of symptoms of GBS. None of the studied cytokines correlated with functional disability scores at admission to hospital or with the electrophysiological subtypes. Identification of Th17 pathway signatures in CSF sheds more insights into the pathogenic role of Th17 cells in GBS. These findings complement the contemporary knowledge and tender further support towards the involvement of Th17 pathway in GBS.


Asunto(s)
Síndrome de Guillain-Barré/líquido cefalorraquídeo , Interleucina-17/líquido cefalorraquídeo , Interleucina-6/líquido cefalorraquídeo , Interleucinas/líquido cefalorraquídeo , Transducción de Señal/fisiología , Células Th17/metabolismo , Adulto , Biomarcadores/líquido cefalorraquídeo , Citocinas/líquido cefalorraquídeo , Citocinas/inmunología , Femenino , Síndrome de Guillain-Barré/inmunología , Humanos , Interleucina-17/inmunología , Interleucina-6/inmunología , Interleucinas/inmunología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Células Th17/inmunología
2.
J Neuroimmunol ; 332: 147-154, 2019 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-31034962

RESUMEN

IL-17 has been implicated in the pathogenesis of multiple sclerosis (MS). Here, we show that blockade of IL-17A, but not IL-17F, attenuated experimental autoimmune encephalomyelitis (EAE). We further show that IL-17A levels were elevated in the CSF of relapsing-remitting MS (RRMS) patients and that they correlated with the CSF/serum albumin quotient (Qalb), a measure of blood-brain barrier (BBB) dysfunction. We then demonstrated that the combination of IL-17A and IL-6 reduced the expression of tight junction (TJ)-associated genes and disrupted monolayer integrity in the BBB cell line hCMEC/D3. However, unlike IL-17A, IL-6 in the CSF from RRMS patients did not correlate with Qalb. These data highlight the potential importance of targeting IL-17A in preserving BBB integrity in RRMS.


Asunto(s)
Barrera Hematoencefálica , Encefalomielitis Autoinmune Experimental/fisiopatología , Interleucina-17/fisiología , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Adulto , Anciano , Animales , Células Cultivadas , Encefalomielitis Autoinmune Experimental/terapia , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Femenino , Humanos , Inmunización Pasiva , Interleucina-17/antagonistas & inhibidores , Interleucina-17/líquido cefalorraquídeo , Interleucina-6/farmacología , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Receptores de Interleucina-6/fisiología , Proteínas Recombinantes/farmacología , Adulto Joven
3.
Acta Biochim Biophys Sin (Shanghai) ; 50(12): 1266-1273, 2018 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-30418472

RESUMEN

Anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis is an autoimmune disorder characterized by memory deficits, psychiatric symptoms, and autonomic instability. The lack of suitable biomarkers targeting anti-NMDAR encephalitis makes the immunotherapy and prognosis challenging. In this study, we found that the Th17 cells were significantly accumulated in the cerebrospinal fluid (CSF) of anti-NMDAR encephalitis patients than that of control individuals. The concentration of the cytokines and chemokines including interleukin (IL)-1ß, IL-17, IL-6, and CXCL-13 were significantly increased in the CSF of anti-NMDAR encephalitis patients. IL-6 and IL-17 were found to promote the differentiation of CD4+ T cells into Th17 lineage. The chemotaxis assay showed that CCL20 and CCL22 play essential roles in the migration of Th17 cells. Notably, the correlation between the expression of IL-17 and the outcome of anti-NMDAR encephalitis patients was analyzed. The data showed that high level of IL-17 was significantly correlated with the limited response to the treatment and relapse of anti-NMDAR encephalitis patients. Our results suggested the potential important involvement of IL-17 in anti-NMDAR encephalitis.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/líquido cefalorraquídeo , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Citocinas/líquido cefalorraquídeo , Células Th17/metabolismo , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/terapia , Linfocitos T CD4-Positivos/metabolismo , Diferenciación Celular/genética , Células Cultivadas , Citocinas/genética , Femenino , Expresión Génica , Humanos , Inmunoterapia/métodos , Interleucina-17/líquido cefalorraquídeo , Interleucina-17/genética , Masculino , Persona de Mediana Edad , Pronóstico
4.
Cytokine ; 108: 160-167, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29625335

RESUMEN

Multiple Sclerosis (MS) and Neuro-Behçet's Disease (NBD) are two recurrent disorders affecting the central nervous system (CNS) by causing inflammation and irreversible damage. Inaugural clinical symptoms for both diseases might be very similar and definitive diagnosis could be delayed. The present study aimed to find out possible differences at early stages in the transcription factors/cytokines expression profiles in blood and cerebrospinal fluid (CSF) of MS and NBD patients which could be useful discriminative markers. Cytokines and transcription factors related to Th1, Th2, Th17 and T regulatory populations were studied by quantitative RT-PCR simultaneously in PBMCs and CSF, from 40 patients presenting a first episode of clinical features related to CNS inflammation and 22 controls with non inflammatory neurological diseases enrolled mainly for severe headache. The follow up of 12 months did allow a definitive diagnosis of remitting relapsing MS (RRMS) in 21 patients and of NBD in the other 19 among those with CNS inflammation compared to controls. In initial blood samples, T-bet was significantly increased in NBD patients only while IFN-γ was elevated in patients who evolved into RRMS or NBD. IL-17a, GATA-3 and IL-4 were significantly lower in RRMS patients than in the NBD group. In initial CSF samples, ROR-γt, IL-17a and IFN-γ were significantly elevated in patients compared to controls. The most striking finding was the significant increase of CSF IL-10 that we did observe in NBD patients only. Thus, we propose CSF IL-10 as a predictive marker to help clinicians discriminating between these two neurological disorders.


Asunto(s)
Síndrome de Behçet/diagnóstico , Interleucina-10/líquido cefalorraquídeo , Esclerosis Múltiple/diagnóstico , Adulto , Biomarcadores/líquido cefalorraquídeo , Barrera Hematoencefálica/inmunología , Sistema Nervioso Central/inmunología , Diagnóstico Diferencial , Femenino , Factor de Transcripción GATA3/líquido cefalorraquídeo , Humanos , Inflamación , Interferón gamma/líquido cefalorraquídeo , Interleucina-17/líquido cefalorraquídeo , Interleucina-4/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/líquido cefalorraquídeo , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/inmunología , Reacción en Cadena en Tiempo Real de la Polimerasa , Células TH1/inmunología , Células Th2/inmunología , Factores de Transcripción/líquido cefalorraquídeo
5.
J Clin Lab Anal ; 32(1)2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28303609

RESUMEN

BACKGROUND: In this study, the pathologies of acute meningitis and encephalopathy were investigated, and biomarkers useful as prognostic indices were searched for. METHODS: The subjects were 31 children with meningitis, 30 with encephalopathy, and 12 with convulsions following gastroenteritis. Control group consisted of 24 children with non-central nervous system infection. Cerebrospinal fluid cytokine analysis was performed. RESULTS: Chemokines significantly increased in the bacterial meningitis group compared with those in viral meningitis and encephalopathy groups. On comparison of interleukin(IL)-17, it increased in cases with status epilepticus in influenza-associated encephalopathy group. In the rotavirus encephalopathy and convulsions following gastroenteritis groups, IL-17 particularly increased in the convulsions following gastroenteritis group. IL-8 increased in all cases irrespective of the causative virus. CONCLUSIONS: In the encephalopathy group, IL-8 may serve as a neurological prognostic index. IL-17 was increased in the convulsions following gastroenteritis group, particularly in cases with status epilepticus, suggesting its involvement as a convulsion-related factor.


Asunto(s)
Biomarcadores/líquido cefalorraquídeo , Encefalopatías/líquido cefalorraquídeo , Quimiocinas/líquido cefalorraquídeo , Interleucina-17/líquido cefalorraquídeo , Meningitis/líquido cefalorraquídeo , Encefalopatías/diagnóstico , Encefalopatías/epidemiología , Estudios de Casos y Controles , Preescolar , Femenino , Humanos , Lactante , Masculino , Meningitis/diagnóstico , Meningitis/epidemiología , Pronóstico
6.
Acta Neurol Scand ; 137(2): 277-282, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29023630

RESUMEN

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system (CNS). Interleukin (IL)-6 and IL-17A may play important roles in the pathogenesis of this disease. High-mobility group box protein 1 (HMGB1), a small but highly conserved ubiquitous protein, is recognized to be a potent innate inflammatory mediator that can activate the nuclear factor light chain enhancer of activated B cells and release cytokines such as IL-6 and IL-17A when released extracellularly. However, whether cerebrospinal fluid (CSF) HMGB1 levels are altered in anti-NMDAR encephalitis is still unclear. OBJECTIVE: The aim of this study was to determine whether a correlation exists between the CSF concentrations of HMGB1 and IL-6 and IL-17A in anti-NMDAR encephalitis patients. We also sought to assess whether HMGB1 influences the clinical outcomes in anti-NMDAR encephalitis patients. METHODS: Thirty-three patients with anti-NMDAR antibodies and 38 controls were recruited. CSF HMGB1 was measured using an enzyme-linked immunosorbent assay. The main clinical outcomes were evaluated using the modified Rankin scale (mRS). The data were extracted using microarray analysis software. RESULTS AND CONCLUSION: Our results showed significant increases in CSF HMGB1, IL-6, and IL-17A (P < .05) in anti-NMDAR encephalitis patients. But between 3 months' mRS scores in anti-NMDAR encephalitis patients and CSF data, there was no correlation. Our study suggests that HMGB1 CSF levels are increased in patients with anti-NMDAR encephalitis and reflect the underlying neuroinflammatory process.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/líquido cefalorraquídeo , Proteína HMGB1/líquido cefalorraquídeo , Interleucina-6/líquido cefalorraquídeo , Adulto , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interleucina-17/líquido cefalorraquídeo , Masculino
7.
Neuromolecular Med ; 19(4): 541-554, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28916896

RESUMEN

The pro-inflammatory activity of interleukin 17, which is produced by the IL-23/IL-17 axis, has been associated with the pathogenesis of traumatic brain injury (TBI). The study investigated the potential role of IL-17 in secondary brain injury of TBI in a rat model. Our data showed that the levels of IL-17 increased from 6 h to 7 days and peaked at 3 days, in both the CNS and serum, which were consistent with the severity of secondary brain injury. The IL-23 inhibitor suberoylanilide hydroxamic acid (SAHA) treatment markedly decreased the expressions of IL-17 and apoptosis-associated proteins cleaved caspase-3 and increased the protein ratio of Bcl-2 (B cell lymphoma/leukemia-2)/Bax (Bcl-2-associated X protein). Meanwhile, neuronal apoptosis was reduced, and neural function was improved after SAHA treatment. This study suggests that IL-17 is involved in secondary brain injury after TBI. Administering an IL-23 inhibitor and thereby blocking the IL-23/IL-17 axis may be beneficial in the treatment of TBI.


Asunto(s)
Daño Encefálico Crónico/fisiopatología , Lesiones Traumáticas del Encéfalo/fisiopatología , Interleucina-17/fisiología , Animales , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/biosíntesis , Proteínas Reguladoras de la Apoptosis/genética , Daño Encefálico Crónico/etiología , Daño Encefálico Crónico/metabolismo , Daño Encefálico Crónico/prevención & control , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Ácidos Hidroxámicos/farmacología , Ácidos Hidroxámicos/uso terapéutico , Inflamación , Interleucina-17/sangre , Interleucina-17/líquido cefalorraquídeo , Interleucina-17/genética , Interleucina-23/antagonistas & inhibidores , Interleucina-23/fisiología , Masculino , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/sangre , Proteínas del Tejido Nervioso/líquido cefalorraquídeo , Proteínas del Tejido Nervioso/genética , Neuronas/patología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Vorinostat
8.
Neurol Res ; 39(6): 552-558, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28441917

RESUMEN

BACKGROUND: Interleukin (IL)-17A was reported to be involved in the development of post-ischemic stroke inflammatory response and functional recovery. However, the IL-17A dynamic changes in serum/cerebrospinal fluid (CSF) and its role in neuronal injury following ischemic stroke are unclear. METHODS: In vivo ischemic stroke was induced by 1 h of middle cerebral artery occlusion (MCAO) and 6 h-7 d reperfusion (R) in mice, while in vitro stroke was induced by 1 h oxygen-glucose deprivation (OGD)/24 h reoxygenation (R) in cultured cortical neurons. Enzyme-linked immunosorbent assay (ELISA) and double-labeled immunofluorescence of IL-17A with neuron (NeuN), astrocyte (GFAP) and microglia (Iba-1)-specific markers were used to determine the IL-17A levels in serum/CSF and neural cell type. RESULTS: The ELISA results showed that IL-17A significantly increased both in peri-infarct region (p < 0.001) and CSF (p < 0.05) following 1 h MCAO/R 12 h. The levels of IL-17A in serum increased at R 1 d (p < 0.05) and peaked at R 3 d (p < 0.001) after 1 h MCAO. Immunofluorescent staining demonstrated that IL-17A co-localized with GFAP in peri-infarct regions. In addition, recombinant rIL-17A could aggravate ischemic injuries at dose-dependent manner in 1 h OGD/R 24 h-treated neurons companying with the increase of IL-17A receptor il-17RA mRNA (p < 0.001) and IL-17R protein levels. CONCLUSION: We firstly reported astrocytic IL-17A peaks in CSF within 12 h and in serum at 3 d reperfusion after ischemic stroke. IL-17A may exaggerate neuronal injuries through its receptor IL-17R at early stage of ischemic stroke.


Asunto(s)
Isquemia Encefálica/metabolismo , Interleucina-17/sangre , Interleucina-17/líquido cefalorraquídeo , Accidente Cerebrovascular/metabolismo , Animales , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media/metabolismo , Masculino , Ratones Endogámicos C57BL , Neuronas/metabolismo , Daño por Reperfusión/metabolismo
9.
J Neuroinflammation ; 14(1): 20, 2017 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-28114998

RESUMEN

BACKGROUND: Steroid-responsive meningitis-arteritis (SRMA) is an immune-mediated disorder characterized by neutrophilic pleocytosis and an arteritis particularly in the cervical leptomeninges. Previous studies of the disease have shown increased levels of IL-6 and TGF-ß1 in cerebrospinal fluid (CSF). In the presence of these cytokines, naive CD4+ cells differentiate into Th17 lymphocytes which synthesize interleukin 17 (IL-17). It has been shown that IL-17 plays an active role in autoimmune diseases, it induces and mediates inflammatory responses and has an important role in recruitment of neutrophils. The hypothesis of a Th17-skewed immune response in SRMA should be supported by evaluating IL-17 and CD40L, inducing the vasculitis. METHODS: An enzyme-linked immunosorbent assay (ELISA) was performed to measure IL-17 and CD40L in serum and CSF from a total of 79 dogs. Measurements of patients suffering from SRMA in the acute state (SRMA A) were compared with levels of patients under treatment with steroids (SRMA T), recurrence of the disease (SRMA R), other neurological disorders, and healthy dogs, using the two-part test. Additionally, secretion of IL-17 and interferon gamma (IFN-γ) from the peripheral blood mononuclear cells (PBMCs) was confirmed by an enzyme-linked immunospot (ELISpot) assay. RESULTS: Significant higher levels of IL-17 were found in CSF of dogs with SRMA A compared with SRMA T, other neurological disorders and healthy dogs (p < 0.0001). In addition, levels of CD40L in CSF in dogs with SRMA A and SRMA R were significantly higher than in those with SRMA T (p = 0.0004) and healthy controls (p = 0.014). Furthermore, CSF concentrations of IL-17 and CD40L showed a strong positive correlation among each other (rSpear = 0.6601; p < 0.0001) and with the degree of pleocytosis (rSpear = 0.8842; p < 0.0001 and rSpear = 0.6649; p < 0.0001, respectively). IL-17 synthesis from PBMCs in SRMA patients was confirmed; however, IL-17 is mainly intrathecally produced. CONCLUSIONS: These results imply that Th17 cells are inducing the autoimmune response in SRMA and are involved in the severe neutrophilic pleocytosis and disruption of the blood-brain barrier (BBB). CD-40L intrathecal synthesis might be involved in the striking vasculitis. The investigation of the role of IL-17 in SRMA might elucidate important pathomechanism and open new therapeutic strategies.


Asunto(s)
Arteritis/tratamiento farmacológico , Ligando de CD40 , Regulación de la Expresión Génica/efectos de los fármacos , Interleucina-17 , Meningitis/tratamiento farmacológico , Esteroides/farmacología , Esteroides/uso terapéutico , Animales , Arteritis/líquido cefalorraquídeo , Ligando de CD40/sangre , Ligando de CD40/líquido cefalorraquídeo , Modelos Animales de Enfermedad , Perros , Ensayo de Inmunoadsorción Enzimática , Interferón gamma/metabolismo , Interleucina-17/sangre , Interleucina-17/líquido cefalorraquídeo , Interleucina-17/metabolismo , Leucocitos Mononucleares/metabolismo , Meningitis/líquido cefalorraquídeo , Estudios Retrospectivos
10.
Bioanalysis ; 8(22): 2317-2327, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27620302

RESUMEN

AIM: IL-17 is thought to play a prominent role in immune disorders. Sensitive and specific IL-17AA and IL-17FF assays were developed and used to determine levels in serum and cerebrospinal fluid (CSF) from patients with rheumatoid arthritis and relapsing remitting multiple sclerosis (RRMS). RESULTS: Qualified assays detected IL-17AA and IL-17FF in healthy and disease samples. Serum IL-17AA was significantly higher in rheumatoid arthritis and RRMS as compared with normal healthy subjects. IL-17AA was also elevated in RRMS CSF as compared with normal healthy subjects; although correlation was observed between serum levels of the two isoforms, no correlation was detected between serum and CSF levels. CONCLUSION: Reliable determination of IL-17 isoforms in the systemic and CNS compartments sheds light on the involvement of IL-17AA and IL-17FF in autoimmunity.


Asunto(s)
Artritis Reumatoide/sangre , Interleucina-17/sangre , Esclerosis Múltiple/sangre , Artritis Reumatoide/líquido cefalorraquídeo , Humanos , Inmunoensayo/métodos , Interleucina-17/líquido cefalorraquídeo , Límite de Detección , Esclerosis Múltiple/líquido cefalorraquídeo , Recurrencia
11.
J Neurol Sci ; 368: 334-6, 2016 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-27538659

RESUMEN

BACKGROUND: Radiologically isolated syndrome (RIS) is a sub clinical demyelinating neurological disorder and to date no biomarker that triggers the seminal event has been identified. As for multiple sclerosis (MS), disease activity and clinical course are unpredictable. In MS, exploratory studies reported increased IL-17 levels in CSF but results in detecting IL-17 in serum at different stage of the disease are controversial. OBJECTIVES: We investigate levels of IL-17 in serum and CSF in patients diagnosed at different stages of demyelinating diseases (RIS, CIS, relapsing remitting (RR) or active multiple sclerosis patients:AMS) as a marker of inflammatory condition. METHODS: 1417 sera has been tested for IL-17A (1177 from active MS, 80 RRMS, 35 RIS, 35 CIS, 10 IIH: idiopathic intracranial hypertension, and 80 controls) and 240 CSF from RIS, CIS, IIH and controls. RESULTS: No difference has been found between RIS who early clinically converted and CIS patients who rapidly evolve in McDonald or clinically definite MS, nor active MS. No correlation was found with usual MRI or CSF criteria. CONCLUSION: Our results do not confirm that IL-17 can be considerate as a reliable marker of inflammation in the demyelinating spectrum disorders, either in blood or CSF.


Asunto(s)
Enfermedades Desmielinizantes/sangre , Enfermedades Desmielinizantes/líquido cefalorraquídeo , Interleucina-17/sangre , Interleucina-17/líquido cefalorraquídeo , Adulto , Enfermedades Desmielinizantes/clasificación , Femenino , Humanos , Masculino , Estudios Prospectivos
13.
J Neuroimmunol ; 297: 141-7, 2016 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-27397087

RESUMEN

The aim of this study was to compare serum and cerebrospinal fluid (CSF) cytokine/chemokine levels between anti-NMDAR and anti-LGI1 encephalitis patients. Samples from fourteen anti-NMDAR encephalitis patients, ten anti-LGI1 encephalitis patients, and ten controls were analyzed for the following cytokines/chemokines: IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17A, IL-23, GM-CSF, IFN-gamma, TNF-alpha, and CXCL13. Compared with controls, CSF IL-17A, IL-6 and CXCL13 were elevated in anti-NMDAR encephalitis patients (post-hoc p-values 0.002, 0.011, and 0.011, respectively) but not in anti-LGI1 encephalitis patients. In the serum, only IL-2 was increased in anti-NMDAR encephalitis. Intrathecal IL-17/IL-6 activation is a characteristic of anti-NMDAR encephalitis.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/líquido cefalorraquídeo , Interleucina-17/líquido cefalorraquídeo , Interleucina-6/líquido cefalorraquídeo , Adolescente , Adulto , Anciano , Encefalitis Antirreceptor N-Metil-D-Aspartato/sangre , Autoanticuerpos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Citocinas/sangre , Citocinas/líquido cefalorraquídeo , Femenino , Glicoproteínas/inmunología , Humanos , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas , Adulto Joven
14.
Genet Mol Res ; 15(2)2016 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-27323066

RESUMEN

To investigate the cytokine profile in serum and cerebrospinal fluid (CSF) from patients with systemic lupus erythematosus (SLE) and central nervous system infection, we measured interferon-g (IFN-g), interleukin-1b (IL-1b), IL-4, IL-6, IL-8, IL-10, and IL-17 levels in serum and CSF from 50 SLE patients and 38 matched controls. In patients with active compared to quiescent disease, serum levels were higher for IL-1b (P = 0.042) and IL-17 (P = 0.041) but we found no significant correlation between IL-1b and IL-17 and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (r = 0.055, r = 0.219, respectively). IL-10 level in active patients was lower compared to that in quiescent controls (P = 0.032). When comparing specific disease manifestations, IL-1b levels in patients with fever (P = 0.035) and IL-6 (P = 0.048) and IL-8 (P = 0.048) levels in those showing nervous system involvement were higher than in controls. Based on MRI results, we found that only increased cerebral ischemia was associated with increased IFN-g levels (P = 0.009). In neuropsychiatric lupus erythematous patients, CSF levels of IL-6 (P = 0.002), IL-8 (P = 0.009), and IL-17 (P = 0.034) were significantly higher when compared with control patients. IL-10:IL-1b ratio in patients with moderate and quiescent disease was higher than in patients with disease activity (P = 0.000). Pro-inflammatory adaptive cytokines were elevated during disease flare, while regulatory mediators were elevated during periods of stable disease. Alterations in the balance between inflammatory and regulatory mediators may be targets for novel immunotherapeutic agents for managing autoimmune diseases.


Asunto(s)
Enfermedades del Sistema Nervioso Central/líquido cefalorraquídeo , Interleucina-17/líquido cefalorraquídeo , Interleucina-6/líquido cefalorraquídeo , Interleucina-8/líquido cefalorraquídeo , Lupus Eritematoso Sistémico/líquido cefalorraquídeo , Anciano , Enfermedades del Sistema Nervioso Central/sangre , Enfermedades del Sistema Nervioso Central/diagnóstico por imagen , Enfermedades del Sistema Nervioso Central/patología , Femenino , Humanos , Interferón gamma/sangre , Interferón gamma/líquido cefalorraquídeo , Interleucina-10/sangre , Interleucina-10/líquido cefalorraquídeo , Interleucina-17/sangre , Interleucina-1beta/sangre , Interleucina-1beta/líquido cefalorraquídeo , Interleucina-4/sangre , Interleucina-4/líquido cefalorraquídeo , Interleucina-6/sangre , Interleucina-8/sangre , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico por imagen , Lupus Eritematoso Sistémico/patología , Masculino , Persona de Mediana Edad
15.
BMC Infect Dis ; 15: 345, 2015 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-26286516

RESUMEN

BACKGROUND: Meningoencephalitis is one of the most common disorders of the central nervous system (CNS) worldwide. Viral meningoencephalitis differs from bacterial meningitis in several aspects. In some developing countries, bacterial meningitis has appropriate clinical management and chemotherapy is available. Virus-associated and virus not detected meningoencephalitis are treatable, however, they may cause death in a few cases. The knowledge of how mediators of inflammation can induce disease would contribute for the design of affordable therapeutic strategies, as well as to the diagnosis of virus not detected and viral meningoencephalitis. Cytokine-induced inflammation to CNS requires several factors that are not fully understood yet. METHODS: Considering this, several cytokines were measured in the cerebrospinal fluid (CSF) of patients with undiagnosed and viral meningoencephalitis, and these were correlated with cellularity in the CSF. RESULTS: The results demonstrate that an altered biochemical profile alongside increased cellularity in the cerebrospinal fluid is a feature of patients with meningoencephalitis that are not associated with the detection of virus in the CNS (P < 0.05). Moreover, HIV-positive patients (n = 10) that evolve with meningoencephalitis display a distinct biochemical/cytological profile (P < 0.05) in the cerebrospinal fluid. Meningoencephalitis brings about a prominent intrathecal cytokine storm regardless of the detection of virus as presumable etiological agent. In the case of Enterovirus infection (n = 13), meningoencephalitis elicits robust intrathecal pro-inflammatory cytokine pattern and elevated cellularity when compared to herpesvirus (n = 15) and Arbovirus (n = 5) viral infections (P < 0.05). CONCLUSION: Differences in the cytokine profile of the CSF may be unique if distinct, viral or presumably non-viral pathways initially trigger the inflammatory response in the CNS.


Asunto(s)
Infecciones por Arbovirus/líquido cefalorraquídeo , Citocinas/líquido cefalorraquídeo , Infecciones por Enterovirus/líquido cefalorraquídeo , Infecciones por VIH/líquido cefalorraquídeo , Infecciones por Herpesviridae/líquido cefalorraquídeo , Infecciones por Lentivirus/líquido cefalorraquídeo , Meningoencefalitis/líquido cefalorraquídeo , Infecciones por Arbovirus/diagnóstico , Infecciones por Arbovirus/inmunología , Enfermedades Virales del Sistema Nervioso Central/líquido cefalorraquídeo , Enfermedades Virales del Sistema Nervioso Central/diagnóstico , Enfermedades Virales del Sistema Nervioso Central/inmunología , Coinfección/líquido cefalorraquídeo , Coinfección/inmunología , Estudios Transversales , Citocinas/inmunología , ADN Viral/líquido cefalorraquídeo , Infecciones por Enterovirus/diagnóstico , Infecciones por Enterovirus/inmunología , Infecciones por VIH/diagnóstico , Infecciones por VIH/inmunología , Infecciones por Herpesviridae/diagnóstico , Infecciones por Herpesviridae/inmunología , Humanos , Inflamación , Interferón gamma/líquido cefalorraquídeo , Interferón gamma/inmunología , Interleucina-10/líquido cefalorraquídeo , Interleucina-10/inmunología , Interleucina-12/líquido cefalorraquídeo , Interleucina-12/inmunología , Interleucina-17/líquido cefalorraquídeo , Interleucina-17/inmunología , Interleucina-6/líquido cefalorraquídeo , Interleucina-6/inmunología , Infecciones por Lentivirus/inmunología , Meningoencefalitis/diagnóstico , Meningoencefalitis/inmunología , ARN Viral/líquido cefalorraquídeo , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeo , Factor de Necrosis Tumoral alfa/inmunología
16.
Clin Immunol ; 157(2): 114-20, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25656641

RESUMEN

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious complication in SLE. Although the mechanism of NPSLE remains unclear, cytokines and chemokines are considered to be involved in their pathogenesis. Here we used Bio-Plex Pro assays to examine 27 types of cytokines and chemokines in the cerebrospinal fluid (CSF) of 32 NPSLE patients. We used the CSF of 20 patients with multiple sclerosis (MS) and 22 patients with neuromyelitis optica (NMO) as a disease control group. Fourteen of 27 cytokines/chemokines were significantly higher in the NPSLE patients compared to the MS/NMO patients. We could identify six "minimum predictive markers" by using a weighted-voting algorithm that could distinguish NPSLE from MS and NMO: interleukin (IL)-17, IL-2, interferon (IFN)-γ, IL-5, basic fibroblast growth factor (FGF)-basic and IL-15. The determination of various types of CSF cytokine profiles may contribute to the diagnosis of NPSLE and may help elucidate the mechanisms underlying this disease.


Asunto(s)
Citocinas/líquido cefalorraquídeo , Vasculitis por Lupus del Sistema Nervioso Central/líquido cefalorraquídeo , Esclerosis Múltiple/líquido cefalorraquídeo , Neuromielitis Óptica/líquido cefalorraquídeo , Adolescente , Adulto , Algoritmos , Estudios de Casos y Controles , Diagnóstico Diferencial , Femenino , Factor 2 de Crecimiento de Fibroblastos/líquido cefalorraquídeo , Humanos , Interferón gamma/líquido cefalorraquídeo , Interleucina-15/líquido cefalorraquídeo , Interleucina-17/líquido cefalorraquídeo , Interleucina-2/líquido cefalorraquídeo , Interleucina-5/líquido cefalorraquídeo , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico , Vasculitis por Lupus del Sistema Nervioso Central/inmunología , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/inmunología , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/inmunología , Sensibilidad y Especificidad , Adulto Joven
17.
PLoS Negl Trop Dis ; 8(7): e3004, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25080350

RESUMEN

BACKGROUND: Treponema pallidum infection evokes vigorous immune responses, resulting in tissue damage. Several studies have demonstrated that IL-17 may be involved in the pathogenesis of syphilis. However, the role of Th17 response in neurosyphilis remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, Th17 in peripheral blood from 103 neurosyphilis patients, 69 syphilis patients without neurological involvement, and 70 healthy donors were analyzed by flow cytometry. The level of IL-17 in cerebrospinal fluid (CSF) was quantified by ELISA. One-year follow up for 44 neurosyphilis patients was further monitored to investigate the role of Th17/IL-17 in neurosyphilis. We found that the frequency of Th17 cells was significantly increased in peripheral blood of patients with neurosyphilis, in comparison to healthy donors. IL-17 in CSF were detected from 55.3% neurosyphilis patients (in average of 2.29 (0-59.83) pg/ml), especially in those with symptomatic neurosyphilis (61.9%). CSF IL-17 was predominantly derived from Th17 cells in neurosyphilis patients. Levels of IL-17 in CSF of neurosyphilis patients were positively associated with total CSF protein levels and CSF VDRL (Venereal Disease Research Laboratory) titers. Notably, neurosyphilis patients with undetectable CSF IL-17 were more likely to confer to CSF VDRL negative after treatment. CONCLUSIONS: These findings indicate that Th17 response may be involved in central nervous system damage and associated with clinical symptoms in neurosyphilis patients. Th17/IL-17 may be used as an alternative surrogate marker for assessing the efficacy of clinical treatment of neurosyphilis patients.


Asunto(s)
Interleucina-17/sangre , Interleucina-17/líquido cefalorraquídeo , Neurosífilis/patología , Treponema pallidum/inmunología , Adolescente , Adulto , Anciano , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Neurosífilis/inmunología , Células Th17/inmunología , Adulto Joven
18.
Scand J Immunol ; 79(3): 181-6, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24383677

RESUMEN

Immunoinflammatory-mediated demyelination, the main pathological feature of multiple sclerosis (MS), is regularly accompanied by neurodegenerative processes, mostly in the form of axonal degeneration, which could be initiated by glutamate excitotoxicity. In the current study, the relationship between Th17-mediated inflammatory and excitotoxic events was investigated during an active phase of MS. Cerebrospinal fluid (CSF) of patients with MS and control subjects was collected, and IL-17A and glutamate levels were determined. IL-17A level was significantly higher in patients with MS; whereas no statistically significant changes in glutamate concentrations were found. There was a direct correlation between IL-17A and glutamate levels; IL-17A levels were also associated with the neutrophil expansion in CSF and blood-brain barrier disruption. However, IL-17A level and the number of neutrophils tended to fall with disease duration. The results suggest that Th17 cells might enhance and use glutamate excitotoxicity as an effector mechanism in the MS pathogenesis. Furthermore, Th17 immune response, as well as neutrophils, could be more important for MS onset rather than further disease development and progression, what could explain why some MS clinical trials, targeting Th17 cells in the later stage of the disease, failed to provide any clinical benefit.


Asunto(s)
Ácido Glutámico/líquido cefalorraquídeo , Interleucina-17/líquido cefalorraquídeo , Esclerosis Múltiple/líquido cefalorraquídeo , Células Th17/inmunología , Adolescente , Adulto , Anciano , Barrera Hematoencefálica/inmunología , Femenino , Ácido Glutámico/metabolismo , Humanos , Inflamación/inmunología , Interleucina-17/metabolismo , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/patología , Neutrófilos/inmunología , Adulto Joven
19.
Arthritis Res Ther ; 15(5): R136, 2013 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-24286492

RESUMEN

INTRODUCTION: The aim of this study was to characterize interleukin 17 (IL-17) and interleukin 22 (IL-22) producing cells in peripheral blood (PB), skin, synovial fluid (SF) and synovial tissue (ST) in patients with psoriasis (Ps) and psoriatic arthritis (PsA). METHODS: Flow cytometry was used to enumerate cells making IL-22 and IL-17, in skin and/or SF and PB from 11 patients with Ps and 12 patients with PsA; skin and PB of 15 healthy controls and SF from rheumatoid arthritis (RA) patients were used as controls. Expression of the interleukin 23 receptor (IL-23R) and chemokine receptors CCR4 and CCR6 was examined. Secretion of IL-17 and IL-22 was measured by ELISA. ST was analysed by immunohistochemical staining of IL-17 and IL-22. RESULTS: Increased frequencies of IL-17+ and IL-22+ CD4+ T cells were seen in PB of patients with PsA and Ps. IL-17 secretion was significantly elevated in both PsA and Ps, whilst IL-22 secretion was higher in PsA compared to Ps and healthy controls. A higher proportion of the CD4+ cells making IL-17 or IL-22 expressed IL-23R and frequencies of IL-17+, CCR6+ and CCR4+ T cells were elevated in patients with Ps and those with PsA. In patients with PsA, CCR6+ and IL-23R + T cells numbers were elevated in SF compared to PB. Increased frequencies of IL-17+ and IL-22+ CD4+ T cells were demonstrated in Ps skin lesions. In contrast, whilst elevated frequencies of CD4+ IL-17+ cells were seen in PsA SF compared to PB, frequencies of CD4+ IL-22+ T cells were lower. Whereas IL-17 expression was equivalent in PsA, osteoarthritis (OA) and RA ST, IL-22 expression was higher in RA than either OA or PsA ST, in which IL-22 was strikingly absent. CONCLUSIONS: Elevated frequencies of IL-17 and IL-22 producing CD4+ T cells were a feature of both Ps and PsA. However their differing distribution at disease sites, including lower frequencies of IL-22+ CD4+ T cells in SF compared to skin and PB, and lack of IL-22 expression in ST suggests that Th17 and Th22 cells have common, as well as divergent roles in the pathogenesis of Ps and PsA.


Asunto(s)
Artritis Psoriásica/inmunología , Psoriasis/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Células Th17/inmunología , Adulto , Anciano , Artritis Psoriásica/metabolismo , Artritis Psoriásica/patología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/patología , Femenino , Citometría de Flujo , Humanos , Inmunohistoquímica , Interleucina-17/sangre , Interleucina-17/líquido cefalorraquídeo , Interleucina-17/inmunología , Interleucinas/sangre , Interleucinas/líquido cefalorraquídeo , Interleucinas/inmunología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/patología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Psoriasis/metabolismo , Psoriasis/patología , Receptores CCR4/inmunología , Receptores CCR4/metabolismo , Receptores CCR6/inmunología , Receptores CCR6/metabolismo , Receptores de Interleucina/inmunología , Receptores de Interleucina/metabolismo , Piel/inmunología , Piel/metabolismo , Piel/patología , Membrana Sinovial/inmunología , Membrana Sinovial/metabolismo , Membrana Sinovial/patología , Linfocitos T Colaboradores-Inductores/metabolismo , Linfocitos T Colaboradores-Inductores/patología , Células Th17/metabolismo , Células Th17/patología
20.
Mediators Inflamm ; 2013: 639712, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24174711

RESUMEN

UNLABELLED: AIMS. Interleukin-37 (IL-37) is an anti-inflammatory cytokine. This study aims to investigate the concentrations of plasma and cerebrospinal fluid (CSF) IL-37 in patients with Guillain-Barré Syndrome (GBS). METHODS: The levels of plasma and CSF IL-37, IL-17A, IFN- γ , and TNF- α in 25 GBS patients and 20 healthy controls (HC) were determined by enzyme-linked immunoabsorbent assay and flow cytometric bead array assay, respectively. The values of clinical parameters in the patients were also measured. RESULTS: The concentrations of plasma IL-37, IL-17A, IFN- γ , and TNF- α and CSF IL-37 and IL-17A in patients at the acute phase of GBS were significantly higher than those in the HC. The levels of plasma IL-37, IL-17A, IFN- γ , and TNF- α were positively correlated in those patients, and the levels of CSF IL-37 and IL-17A as well as the levels of plasma TNF- α were correlated positively with the GBS disability scale scores (GDSs) in those patients. Treatment with intravenous immunoglobulin significantly reduced the levels of plasma IL-37, IL-17A, IFN- γ , and TNF- α in the drug-responding patients. CONCLUSIONS: Our findings indicate higher levels of plasma and CSF IL-37 and IL-17A and other proinflammatory cytokines in patients with GBS.


Asunto(s)
Síndrome de Guillain-Barré/sangre , Síndrome de Guillain-Barré/líquido cefalorraquídeo , Interleucina-1/sangre , Interleucina-1/líquido cefalorraquídeo , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Regulación de la Expresión Génica , Humanos , Inmunoglobulinas/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Inflamación/metabolismo , Interferón gamma/sangre , Interferón gamma/líquido cefalorraquídeo , Interleucina-17/sangre , Interleucina-17/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeo , Adulto Joven
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